KCTD1

Summary

KCTD1 (potassium channel tetramerization domain containing 1, HGNC:18249) is a protein-coding gene on chromosome 18q11.2, encoding BTB/POZ domain-containing protein KCTD1 (Q719H9). May repress the transcriptional activity of AP-2 family members, including TFAP2A, TFAP2B and TFAP2C to various extent.

This gene encodes a protein containing a BTB (Broad-complex, tramtrack and bric a brac), also known as a POZ (POxvirus and zinc finger) protein-protein interaction domain. The encoded protein negatively regulates the AP-2 family of transcription factors and the Wnt signaling pathway. A mechanism for the modulation of Wnt signaling has been proposed in which the encoded protein enhances ubiquitination and degradation of the beta-catenin protein. Mutations in this gene have been identified in Scalp-ear-nipple (SEN) syndrome.

Source: NCBI Gene 284252 — RefSeq curated summary.

At a glance

• Gene–disease (curated): scalp-ear-nipple syndrome (Strong, GenCC)
• GWAS associations: 83
• Clinical variants (ClinVar): 228 total — 15 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 82
• MANE Select transcript: NM_001142730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18249
Approved symbol	KCTD1
Name	potassium channel tetramerization domain containing 1
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134504
Ensembl biotype	protein_coding
OMIM	613420
Entrez	284252

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000317932, ENST00000408011, ENST00000417602, ENST00000577255, ENST00000578973, ENST00000579973, ENST00000580059, ENST00000580191, ENST00000580638, ENST00000582494, ENST00000584630, ENST00000890172

RefSeq mRNA: 6 — MANE Select: NM_001142730 NM_001136205, NM_001142730, NM_001258221, NM_001258222, NM_001351443, NM_198991

CCDS: CCDS11888

Canonical transcript exons

ENST00000580059 — 5 exons

Exon	Start	End
ENSE00001177928	26476515	26476659
ENSE00001912879	26454910	26455901
ENSE00002722501	26546728	26548553
ENSE00003477920	26501072	26501250
ENSE00003502555	26459620	26459925

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0976 / max 229.6578, expressed in 1648 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171441	7.8473	1630
171445	2.0766	647
171449	1.3324	840
171453	0.3592	185
171442	0.3484	148
171452	0.3316	193
171444	0.3148	119
171446	0.1977	73
171447	0.1444	61
171443	0.0600	14

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	98.65	gold quality
upper arm skin	UBERON:0004263	96.68	gold quality
penis	UBERON:0000989	95.70	gold quality
mammalian vulva	UBERON:0000997	95.40	gold quality
prefrontal cortex	UBERON:0000451	94.95	gold quality
upper leg skin	UBERON:0004262	94.88	gold quality
middle temporal gyrus	UBERON:0002771	94.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.84	gold quality
putamen	UBERON:0001874	94.81	gold quality
superior frontal gyrus	UBERON:0002661	94.62	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.51	gold quality
postcentral gyrus	UBERON:0002581	94.50	gold quality
right uterine tube	UBERON:0001302	94.42	gold quality
parietal lobe	UBERON:0001872	94.39	gold quality
frontal cortex	UBERON:0001870	94.38	gold quality
caudate nucleus	UBERON:0001873	94.38	gold quality
pharyngeal mucosa	UBERON:0000355	94.22	gold quality
right frontal lobe	UBERON:0002810	93.94	gold quality
primary visual cortex	UBERON:0002436	93.90	gold quality
kidney epithelium	UBERON:0004819	93.90	gold quality
neocortex	UBERON:0001950	93.77	gold quality
nucleus accumbens	UBERON:0001882	93.75	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.41	gold quality
occipital lobe	UBERON:0002021	93.38	gold quality
esophagus mucosa	UBERON:0002469	93.34	gold quality
nipple	UBERON:0002030	93.32	gold quality
cerebral cortex	UBERON:0000956	92.86	gold quality
skin of abdomen	UBERON:0001416	92.62	gold quality
fallopian tube	UBERON:0003889	92.57	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	91.04
E-CURD-119	yes	44.07
E-ANND-3	yes	8.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TFAP2A

miRNA regulators (miRDB)

92 targeting KCTD1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-448	99.79	72.37	2103

Literature-anchored findings (GeneRIF, showing 11)

• indicate the novel function of KCTD1 as the transcriptional repressor for AP-2 family, especially for AP-2alpha (PMID:19115315)
• Mutations in KCTD1 cause scalp-ear-nipple syndrome. (PMID:23541344)
• The authors find that the KCTD proteins 5, 6, 9 and 17 bind to Cul3 with high affinity, while the KCTD proteins 1 and 16 do not have detectable binding. (PMID:26334369)
• results reveal a novel role for Cu(2+) in determining the structure and function of KCTD1 (PMID:27596723)
• Molecular basis of the scalp-ear-nipple syndrome unraveled by the characterization of disease-causing KCTD1 mutants. (PMID:31324836)
• AP-2beta/KCTD1 Control Distal Nephron Differentiation and Protect against Renal Fibrosis. (PMID:32553120)
• KCTD1 mutants in scalpearnipple syndrome and AP2alpha P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/betacatenin signaling. (PMID:33000225)
• Magnesium and Calcium Homeostasis Depend on KCTD1 Function in the Distal Nephron. (PMID:33440155)
• KCTD1/KCTD15 complexes control ectodermal and neural crest cell functions, and their impairment causes aplasia cutis. (PMID:38113115)
• Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies. (PMID:38791218)
• Structural studies of KCTD1 and its disease-causing mutant P20S provide insights into the protein function and misfunction. (PMID:39111466)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd1	ENSDARG00000074056
mus_musculus	Kctd1	ENSMUSG00000036225
rattus_norvegicus	Kctd1	ENSRNOG00000016467
drosophila_melanogaster	twz	FBGN0034636
caenorhabditis_elegans	F32B4.5	WBGENE00009315

Paralogs (13): KCTD14 (ENSG00000151364), KCTD15 (ENSG00000153885), KCTD18 (ENSG00000155729), KCTD6 (ENSG00000168301), KCTD19 (ENSG00000168676), KCTD12 (ENSG00000178695), KCTD4 (ENSG00000180332), KCTD16 (ENSG00000183775), KCTD8 (ENSG00000183783), KCTD21 (ENSG00000188997), KCNRG (ENSG00000198553), KCTD11 (ENSG00000213859), KCTD7 (ENSG00000243335)

Protein

Protein identifiers

BTB/POZ domain-containing protein KCTD1 — Q719H9 (reviewed: Q719H9)

Alternative names: Potassium channel tetramerization domain-containing protein 1

All UniProt accessions (5): Q719H9, A0A2U3U043, J3KSG1, J3QLL6, J3QRK1

UniProt curated annotations — full annotation on UniProt →

Function. May repress the transcriptional activity of AP-2 family members, including TFAP2A, TFAP2B and TFAP2C to various extent.

Subunit / interactions. Forms homopentamers (Ref.10). Interacts with KCTD15, probably forming heteropentamers depending on its abundance in a cell-type dependent manner. Interacts with TFAP2A, TFAP2B and TFAP2C via the BTB domain.

Subcellular location. Nucleus.

Tissue specificity. Expressed in mammary gland, kidney, brain and ovary.

Post-translational modifications. Sumoylated.

Disease relevance. Scalp-ear-nipple syndrome (SENS) [MIM:181270] A disease characterized by aplasia cutis congenita of the scalp, breast anomalies that range from hypothelia or athelia to amastia, and minor anomalies of the external ears. Less frequent clinical characteristics include nail dystrophy, dental anomalies, cutaneous syndactyly of the digits, and renal malformations. Penetrance appears to be high, although there is substantial variable expressivity within families. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (6): NP_001129677, NP_001136202, NP_001245150, NP_001245151, NP_001338372, NP_945342 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR048595	KCTD1-15-like_C	Domain
IPR048599	BTB_POZ_KCTD1	Domain

Pfam: PF02214, PF20871

UniProt features (38 total): strand 11, sequence variant 9, helix 8, turn 3, modified residue 2, chain 1, domain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5BXD	X-RAY DIFFRACTION	1.8
5BXB	X-RAY DIFFRACTION	2.17
6S4L	X-RAY DIFFRACTION	2.42
9FQ1	X-RAY DIFFRACTION	2.6
9FOI	X-RAY DIFFRACTION	2.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q719H9-F1	87.67	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 9, 12

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8866904	Negative regulation of activity of TFAP2 (AP-2) family transcription factors
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors

MSigDB gene sets: 294 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, AAGCCAT_MIR135A_MIR135B, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, AAAGGGA_MIR204_MIR211, GOBP_PROTEIN_HOMOOLIGOMERIZATION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chr18q11, GOMF_TRANSCRIPTION_FACTOR_BINDING, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, LEE_BMP2_TARGETS_UP, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_DN, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3

GO Biological Process (2): negative regulation of DNA-templated transcription (GO:0045892), protein homooligomerization (GO:0051260)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), transcription factor binding (GO:0008134), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), centriolar satellite (GO:0034451), intercellular bridge (GO:0045171)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	2
nuclear lumen	2
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
protein complex oligomerization	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1
centrosome	1

Protein interactions and networks

STRING

398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD1	TFAP2A	P05549	876
KCTD1	TFAP2C	Q92754	810
KCTD1	TFAP2B	Q92481	789
KCTD1	KCTD9	Q7L273	697
KCTD1	KCTD5	Q9NXV2	671
KCTD1	CUL3	Q13618	645
KCTD1	BTBD10	Q9BSF8	635
KCTD1	KCTD20	Q7Z5Y7	541
KCTD1	HDAC1	Q13547	486
KCTD1	ZNF841	Q6ZN19	433
KCTD1	TRIM43B	A6NCK2	431
KCTD1	BICC1	Q9H694	412
KCTD1	PPHLN1	Q8NEY8	390
KCTD1	ZNF432	O94892	366
KCTD1	ATF7IP	Q6VMQ6	351

IntAct

96 interactions, top by confidence:

A	B	Type	Score
KCTD1	LNX1	psi-mi:“MI:0915”(physical association)	0.780
KCTD1	KCTD1	psi-mi:“MI:0915”(physical association)	0.770
KCTD1	KCTD1	psi-mi:“MI:0407”(direct interaction)	0.770
SDCBP	KCTD1	psi-mi:“MI:0915”(physical association)	0.720
KCTD1	POLR1C	psi-mi:“MI:0915”(physical association)	0.720
EXOSC1	KCTD1	psi-mi:“MI:0915”(physical association)	0.720
KCTD1	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
POLR1C	KCTD1	psi-mi:“MI:0915”(physical association)	0.720
KCTD1	EXOSC1	psi-mi:“MI:0915”(physical association)	0.720
KCTD1	NTAQ1	psi-mi:“MI:0915”(physical association)	0.670
KCTD1	TRAPPC2	psi-mi:“MI:0915”(physical association)	0.560
ZBTB25	KCTD1	psi-mi:“MI:0915”(physical association)	0.560
KCTD1	PSMA1	psi-mi:“MI:0915”(physical association)	0.560
PRKAA2	KCTD1	psi-mi:“MI:0915”(physical association)	0.560
UBE2I	KCTD1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (73): KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), KCTD1 (Two-hybrid), UBE2I (Two-hybrid)

ESM2 similar proteins: A3KMV1, A4IFB4, A5PKG7, A9ULR9, B1WC97, B5DEL1, O70479, O73916, P0C5J9, Q01820, Q0VD00, Q0VFV7, Q12259, Q13829, Q28DC9, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q5EAX2, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q6DC02, Q6DCX3, Q6DG99, Q6P3P4, Q6P7W2, Q719H9, Q7TNY1, Q7TPL3, Q7Z3E5, Q863D4, Q8BGV7, Q8BJK1, Q8BNL5, Q8K0E1

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, B1WC97, B5DEL1, D5SHR0, G5EFC3, O65555, P0C5J9, P15388, P17971, P17972, P25122, P48547, P59994, P59995, Q01956, Q03607, Q03719, Q0VD00, Q0VFV7, Q14003, Q14681, Q29RJ0, Q2HJ48, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q52PG9, Q54KH0, Q5DTY9, Q5M956, Q5XJ34, Q5ZJP7, Q62897, Q63881, Q63959, Q68DU8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

228 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	3
Uncertain significance	150
Likely benign	31
Benign	19

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
235827	NM_001142730.3(KCTD1):c.2031C>A (p.Asp677Glu)	Pathogenic
235828	NM_001142730.3(KCTD1):c.1882C>T (p.Pro628Ser)	Pathogenic
280853	NM_001142730.3(KCTD1):c.1921C>T (p.His641Tyr)	Pathogenic
4533333	I66F	Pathogenic
4533334	KCTD1, 3-BP INS, 186GTT	Pathogenic
4533335	G62V	Pathogenic
4533336	KCTD1, ARG241GLN (rs776466895)	Pathogenic
4533337	KCTD1, PRO243SER	Pathogenic
55881	NM_001142730.3(KCTD1):c.1913C>A (p.Ala638Glu)	Pathogenic
55882	NM_001142730.3(KCTD1):c.1916C>G (p.Pro639Arg)	Pathogenic
55883	NM_001142730.3(KCTD1):c.1916C>T (p.Pro639Leu)	Pathogenic
55884	NM_001142730.3(KCTD1):c.1916C>A (p.Pro639His)	Pathogenic
55885	NM_001142730.3(KCTD1):c.1923C>A (p.His641Gln)	Pathogenic
55886	NM_001142730.3(KCTD1):c.1922A>C (p.His641Pro)	Pathogenic
55887	NM_001142730.3(KCTD1):c.2045A>C (p.His682Pro)	Pathogenic
3254677	NM_001142730.3(KCTD1):c.2056G>C (p.Asp686His)	Likely pathogenic
3901546	NM_001142730.3(KCTD1):c.2020A>T (p.Ile674Phe)	Likely pathogenic
55888	NM_001142730.3(KCTD1):c.2009G>A (p.Gly670Asp)	Likely pathogenic

SpliceAI

2066 predictions. Top by Δscore:

Variant	Effect	Δscore
18:26455898:GGAC:G	acceptor_gain	1.0000
18:26455899:GACCT:G	acceptor_loss	1.0000
18:26455900:ACC:A	acceptor_loss	1.0000
18:26455902:C:CA	acceptor_loss	1.0000
18:26455902:C:CC	acceptor_gain	1.0000
18:26476509:CCTCA:C	donor_loss	1.0000
18:26476510:CTCA:C	donor_loss	1.0000
18:26476511:TCA:T	donor_loss	1.0000
18:26476512:CAC:C	donor_loss	1.0000
18:26476514:C:CA	donor_loss	1.0000
18:26476658:TT:T	acceptor_gain	1.0000
18:26476660:C:CC	acceptor_gain	1.0000
18:26501068:TTA:T	donor_loss	1.0000
18:26501069:TA:T	donor_loss	1.0000
18:26501070:AC:A	donor_loss	1.0000
18:26501246:CTGTC:C	acceptor_gain	1.0000
18:26501247:TGTC:T	acceptor_gain	1.0000
18:26501249:TC:T	acceptor_gain	1.0000
18:26501250:CC:C	acceptor_gain	1.0000
18:26501251:C:CC	acceptor_gain	1.0000
18:26455899:GAC:G	acceptor_gain	0.9900
18:26455900:AC:A	acceptor_gain	0.9900
18:26455901:CC:C	acceptor_gain	0.9900
18:26455905:C:CT	acceptor_gain	0.9900
18:26459615:TATA:T	donor_loss	0.9900
18:26459618:A:C	donor_loss	0.9900
18:26459619:C:T	donor_loss	0.9900
18:26459924:TCCTG:T	acceptor_loss	0.9900
18:26459926:C:CA	acceptor_loss	0.9900
18:26459927:T:A	acceptor_loss	0.9900

AlphaMissense

5664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:26455827:G:C	F230L	1.000
18:26455827:G:T	F230L	1.000
18:26455829:A:G	F230L	1.000
18:26455852:C:T	G222E	1.000
18:26459651:A:G	L195P	1.000
18:26459651:A:T	L195Q	1.000
18:26459656:A:C	F193L	1.000
18:26459656:A:T	F193L	1.000
18:26459657:A:G	F193S	1.000
18:26459658:A:G	F193L	1.000
18:26459660:C:A	R192M	1.000
18:26459666:A:T	V190D	1.000
18:26459688:A:G	W183R	1.000
18:26459688:A:T	W183R	1.000
18:26459732:A:G	F168S	1.000
18:26459759:C:T	G159D	1.000
18:26459760:C:G	G159R	1.000
18:26459761:G:C	S158R	1.000
18:26459761:G:T	S158R	1.000
18:26459763:T:G	S158R	1.000
18:26459885:A:G	L117P	1.000
18:26459891:A:G	F115S	1.000
18:26459901:C:G	A112P	1.000
18:26459903:T:A	E111V	1.000
18:26459904:C:T	E111K	1.000
18:26459912:A:G	L108S	1.000
18:26476549:C:A	R92L	1.000
18:26476549:C:G	R92P	1.000
18:26476549:C:T	R92Q	1.000
18:26476550:G:C	R92G	1.000

dbSNP variants (sampled 300 via entrez): RS1000004907 (18:26656537 G>A), RS1000033781 (18:26595921 T>A), RS1000041521 (18:26565941 A>G), RS1000044517 (18:26479415 A>C,T), RS1000050156 (18:26540600 C>T), RS1000050440 (18:26641077 C>A), RS1000061266 (18:26503875 G>C), RS1000072682 (18:26565421 T>C), RS1000086497 (18:26605687 C>T), RS1000116550 (18:26656387 G>A,T), RS1000124085 (18:26550717 C>G), RS1000129241 (18:26656497 G>A), RS1000147581 (18:26464805 G>A), RS1000166505 (18:26532100 A>G), RS1000180676 (18:26464487 C>T)

Disease associations

OMIM: gene MIM:613420 | disease phenotypes: MIM:181270, MIM:621434

GenCC curated gene-disease

Disease	Classification	Inheritance
scalp-ear-nipple syndrome	Strong	Autosomal dominant

Mondo (2): scalp-ear-nipple syndrome (MONDO:0008404), dental radicular dysplasia (MONDO:0980763)

Orphanet (1): Scalp-ear-nipple syndrome (Orphanet:2036)

HPO phenotypes

82 total (30 of 82 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000073	Ureteral duplication
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000122	Unilateral renal agenesis
HP:0000164	Abnormality of the dentition
HP:0000193	Bifid uvula
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000378	Cupped ear
HP:0000385	Small earlobe
HP:0000396	Overfolded helix
HP:0000411	Protruding ear
HP:0000463	Anteverted nares
HP:0000506	Telecanthus
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000581	Blepharophimosis
HP:0000601	Hypotelorism
HP:0000612	Iris coloboma
HP:0000625	Eyelid coloboma
HP:0000652	Lower eyelid coloboma
HP:0000679	Taurodontia
HP:0000684	Delayed eruption of teeth
HP:0000691	Microdontia
HP:0000822	Hypertension

GWAS associations

83 associations (top):

Study	Trait	p-value
GCST001099_25	Sudden cardiac arrest	8.000000e-10
GCST004862_114	Itch intensity from mosquito bite adjusted by bite size	4.000000e-06
GCST005352_19	Paclitaxel disposition in epithelial ovarian cancer	3.000000e-06
GCST007876_69	Estimated glomerular filtration rate	4.000000e-12
GCST010796_2963	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-19
GCST010796_2964	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_2965	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_2966	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-11
GCST010796_2967	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010796_2968	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-10
GCST010796_2969	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_2970	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_2971	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-12
GCST010796_2972	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12
GCST010796_2973	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_2974	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-15
GCST010796_2975	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-15
GCST010796_2976	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_2977	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_2978	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-14
GCST010796_2979	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-14
GCST010796_2980	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_2981	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-13
GCST010796_2982	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-13
GCST010796_2983	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-13
GCST010796_2984	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-15
GCST010796_2985	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_2986	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-16
GCST010796_2987	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_2988	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536623	Scalp ear nipple syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Methapyrilene	increases methylation	1
Silicon Dioxide	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.